The present disclosure provides compositions and methods useful for treating Glioblastoma Multiforme (GBM), e.g., compositions comprising virus-like particles (VLPs) comprising Moloney Murine leukemia virus (MMLV) core proteins and the human cytomegalovirus epitopes, gB and pp65, formulated with GM-CSF, which, at dose of at least 10 g gB/pp65Gag, reverse dysregulation of anti-HCMV immunity in GBM patients.

Peptides that generate an immune response to glioma-related H3.3 proteins and methods of their use are provided.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention is directed to immune adjuvants containing IAP inhibitors, including Smac mimetics. The invention further provides pharmaceutical compositions and vaccines containing an IAP inhibitor and an antigen. Methods of enhancing an immune response by administration of an IAP inhibitor, methods of treating or preventing cancer, methods of treating or preventing infections, methods of treating autoimmune disorders, and methods of potentiating cytokine or antibody production are also provided.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Disclosed herein are methods of treating a brain cancer comprising administering to a subject in need thereof a viral composition comprising a flavivirus or portion of a flavivirus wherein the flavivirus is engineered to comprise a heterologous nucleic acid sequence encoding a suicide gene. In some embodiments, the brain cancer is selected from the group consisting of astrocytoma, oligodendroglioma, ependymoma, meningioma, schwannoma, craniopharyngioma, germinoma, and pineocytoma. In some embodiments the flavivirus comprises Zika virus, spondweni virus, kedougous virus, or a combination thereof. In some embodiments, the flavivirus comprises Zika virus. In some embodiments, the suicide gene encodes a protein that converts a prodrug into a cytotoxic agent. In some embodiments, the viral composition is administered in combination with the immunostimulatory agent.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

This invention provides new compositions comprising nucleotide sequence(s) encoding alphaherpesvirus glycoprotein D protein(s) (gDP(s)) and antigen(s) that induce immune responses. Such sequences typically encode gDP:antigen fusion proteins and typically also include feature(s) that significantly enhance immune responses such as (a) sequences encoding ITIC signal transducing adaptor proteins, e.g., SLAM-associated proteins (SAPs), Ewing's sarcoma-associated transcript 2 proteins, or both, or non-gDP checkpoint inhibitor(s); (b) sequences encoding antigen-associated targeting sequences, e.g., polyubiquitin sequences; (c) deimmunized/modified antigen-encoding sequences; (d) gDP(s) with modified sequence(s); (e) expression-enhancing introns; (f) transfection-facilitating agents; or (g) combinations thereof. Methods of using such constructs to induce immune responses and other methods and compositions also are provided, including methods of using such constructs in animals not known to express Herpesvirus entry mediator (HVEM) receptors (e.g., pigs), animals not under disease agent-associated checkpoint inhibition, and other contexts.

This disclosure relates to a monoclonal antibody directed against CD73 or an antigen-binding fragment thereof, and the use of such antibody or antigen-binding fragment thereof in the treatment of tumors. The disclosure also relates to methods for the treatment of tumors comprising administering to a patient in need thereof an anti-CD73 antibody or antigen-binding fragment thereof in combination with a monoclonal antibody directed against programmed death-ligand 1 (PD-L1) also known as B7 homolog 1 (B7-H1), or an antigen-binding fragment thereof. The disclosure also relates to methods for the treatment of tumors comprising administering to a patient in need thereof an anti-CD73 antibody or antigen-binding fragment thereof in combination with a PD-L1 antibody or an antigen-binding fragment thereof and chemotherapy.

Anti-CD223 antibodies overcome immune suppression in cancer patients. The anti-CD223 antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.